Rhinovirus infections are the predominant cause of the common cold (18), the most frequently experienced acute respiratory illness in humans. Recent evidence also implicates rhinovirus infections as an important precipitating factor for exacerbations of asthma (21, 22, 37), chronic bronchitis (35), sinusitis (19, 50), and otitis media (3). Despite the high health care costs associated with rhinovirus infections, the underlying process by which viral infection leads to symptomatology is poorly understood.
The epithelial cell is the primary site of rhinovirus infection (6, 51). In contrast to other respiratory viruses, such as influenza, cytotoxic damage of infected epithelial cells does not appear to play a role in the pathogenesis of rhinovirus infections, since cytotoxicity is not observed either in infected human epithelial cell cultures (49) or in the nasal mucosa of infected individuals (53, 54). In light of this, emphasis has focused on the concept that symptoms may result from the actions of proinflammatory mediators that are generated as a consequence of rhinovirus infection. Support for this hypothesis has come from two lines of evidence: 1) Studies of subjects with experimentally-induced, or naturally-acquired colds have demonstrated increased levels of several mediators, including kinins (36, 41), IL-1 (40), and IL-6 (55) in nasal secretions during symptomatic rhinovirus infections, and 2) infection of purified human respiratory epithelial cell populations with rhinovirus has been shown to induce production of proinflammatory cytokines, including IL-8, IL-6 and GM-CSF (49, 55), that could contribute to disease pathogenesis. To date, however, the specific biochemical events involved in the production of each of these cytokines by rhinoviruses are incompletely understood, and the role of specific cytokines, and other mediators, in the pathogenesis of colds remains to be established.